Novel Relationship Between Plasmalogen Lipid Signatures and Carnosine in Humans

Introduction Carnosine is a naturally occurring dipeptide abundant in the skeletal and cardiac muscle and brain, which has been shown to improve glucose metabolism and cardiovascular risk. This study showed that carnosine supplementation had positive changes on plasma lipidome. Here, this study aimed to establish the relationship of muscle carnosine and serum carnosinase-1 with cardiometabolic risk factors and the lipidome. Methods and Results This study profiles >450 lipid species in 65 overweight/obese nondiabetic individuals. Intensive metabolic testing is conducted using direct gold-standard measures of adiposity, insulin sensitivity and secretion, as well as measurement of serum inflammatory cytokines and adipokines. Muscle carnosine is negatively associated with 2-h glucose concentrations, whereas serum carnosinase-1 levels are negatively associated with insulin sensitivity and positively with IL-18. O-PLS and machine learning analyses reveal a strong association of muscle carnosine with ether lipids, particularly arachidonic acid-containing plasmalogens. Carnosinase-1 levels are positively associated with total phosphatidylethanolamines, but negatively with lysoalkylphosphatidylcholines, trihexosylceramides, and gangliosides. In particular, alkylphosphatidylethanolamine species containing arachidonic acid are positively associated with carnosinase-1. Conclusion These associations reinforce the role of muscle carnosine and serum carnosinase-1 in the interplay among low-grade chronic inflammation, glucose homeostasis, and insulin sensitivity This studyhas been funded by Instituto de Salud Carlos III through the project“PI18/01022” (Co-funded by European Regional Development Fund “Away to make Europe”). This work was supported by the National Healthand Medical Research Council (NHMRC) of Australia (APP1047897). JordiMayneris-Perxachs is funded by the Miguel Servet Program from the Insti-tuto de Salud Carlos III (ISCIII CP18/00009), co-funded by the EuropeanSocial Fund “Investing in your future.” A.M. is supported by a Peter Do-herty Biomedical Research Fellowship provided by the NHMRC. N.N. isa Monash Partners Health Services Research Fellow. B.dC. is supportedby a Royal Australasian College of Physicians Fellows Career DevelopmentFellowship. and is the recipient of the NHMRC grant, which funded thisstudy Open Access funding provided thanks to the CRUE-CSIC agreement with Wiley